Chronic NMDA Antagonism Impairs Working Memory, Decreases Extracellular Dopamine, and Increases D1 Receptor Binding in Prefrontal Cortex of Conscious Monkeys

Tsukada, Hideo; Nishiyama, Shingo; Fukumoto, Dai; Sato, Kengo; Kakiuchi, Takeharu; Domino, Edward F.

doi:10.1038/sj.npp.1300732

Cited by 84 publications

(80 citation statements)

References 63 publications

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“…PET studies have suggested that dysfunction of the extrastriatal dopaminergic system exists in schizophrenic patients (Okubo et al, 1997;Lindström et al, 1999;Abi-Dargham et al, 2002;Suhara et al, 2002;Laruelle et al, 2003). We have found that acute and chronic NMDA antagonism impairs cognitive function through different modulations in the dopaminergic neuronal system in the PFC of monkeys (Tsukada et al, 2005). Thus, acute systemic administration of low doses (0.03 and (Tsukada et al, 2005).…”

Section: Discussionmentioning

confidence: 92%

“…In order to induce dysfunction of the PFC dopaminergic neuronal system, as previously reported (Tsukada et al, 2005), MK-801 at a dose of 0.03 mg/kg was administered intramuscularly (i.m.) twice a day for 13 days.…”

Section: Drug Treatmentsmentioning

confidence: 99%

“…Behavioral task performance was evaluated as described previously (Inoue et al, 2004;Tsukada et al, 2004Tsukada et al, , 2005. Briefly, in the oculomotor delayed response (ODR) task, after a short inter-trial interval (ITI), a small red spot (0.11 in diameter) appeared as a fixation point at the center of a 15-in monitor placed in front of the monkey 57 cm from its face.…”

Section: Behavioral Tasksmentioning

confidence: 99%

“…These effects on animals have been used as a model for psychosis in humans. We have previously reported that chronic administration of MK-801 in monkeys impairs working memory performance, which is closely related to functions of the PFC (Tsukada et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, [ 11 C]NNC112 (Halldin et al, 1998) and [ 11 C]FLB457 (Halldin et al, 1995) have been developed to assess extrastriatal DA D 1 (D 1 R) and D 2 receptors (D 2 R), respectively. Both radioligands have enough high affinity to assess the lower density of DA receptors in extrastriatal regions (Hall et al, 1988;Lidow et al, 1989 (Tsukada et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Nicotine Normalizes Increased Prefrontal Cortical Dopamine D1 Receptor Binding and Decreased Working Memory Performance Produced by Repeated Pretreatment with MK-801: A PET Study in Conscious Monkeys

Tsukada

Miyasato

Nishiyama

et al. 2005

Neuropsychopharmacol

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Section: Discussionmentioning

confidence: 92%

Section: Drug Treatmentsmentioning

confidence: 99%

Section: Behavioral Tasksmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Nicotine Normalizes Increased Prefrontal Cortical Dopamine D1 Receptor Binding and Decreased Working Memory Performance Produced by Repeated Pretreatment with MK-801: A PET Study in Conscious Monkeys

Tsukada

Miyasato

Nishiyama

et al. 2005

Neuropsychopharmacol

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Learning large‐scale spatial relationships in a maze and effects of MK‐801 on retrieval in the rhesus monkey

Wang

Zhang

Meng

et al. 2007

Developmental Neurobiology

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Monkeys have strong abilities to remember the visual properties of potential food sources for survival in the nature. The present study demonstrated the first observations of rhesus monkeys learning to solve complex spatial mazes in which routes were guided by visual cues. Three monkeys were trained in a maze (6 m x 6 m) included of four different mazes. We recorded the cue and cup errors, latencies, and pathway for each trial. The data showed that monkeys learned the target place after three days in the first maze and spent a shorter time in learning the following mazes. The maze was an efficient method to measure the ability and proceeding of spatial memory in monkeys. Moreover, working memory can also be tested by using the maze. MK-801 at 0.02 mg/kg but not at 0.005 mg/kg impaired monkeys' retrieval of spatial memory after they learned all four mazes. The present maze may provide an efficient method to help bridging the gap in cognition between nonhuman primates and humans, and in particular to gain insight into human cognitive function and dysfunction.

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Effect of intermittent subchronic MK‐801 administration on dopamine synthesis capacity and responsiveness in the prefrontal cortex

Shibata,

Enomoto,

Tsutsumi

et al. 2024

Neuropsychopharm Rep

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AimThe therapeutic potential of N‐methyl‐D‐aspartate glutamate receptor (NMDAR) antagonists, particularly ketamine, in mood disorders, is linked to their modulation of dopamine dynamics in the medial prefrontal cortex (mPFC). However, conflicting effects of distinct NMDAR antagonists, like ketamine and phencyclidine, on mPFC dopamine levels stem from variances in their receptor affinity profiles. This study investigates the impact of intermittent subchronic administration of an NMDAR antagonist on dopamine synthesis capacity and responsiveness within the mPFC, focusing on Dizocilpine (MK‐801), a highly selective NMDAR antagonist.MethodsIn vivo microdialysis and high‐performance liquid chromatography assessed extracellular dopamine levels in the mPFC following subchronic MK‐801 treatment. Locomotor activity was measured using a computed video tracking system.ResultsIntermittent subchronic MK‐801 administration, followed by a 24‐h withdrawal, preserved both dopamine synthesis capacity and responsiveness to MK‐801 challenge in the mPFC. However, altered locomotor activity was observed, deviating from previous findings indicating impaired dopamine synthesis and responsiveness in the mPFC with twice‐daily subchronic NMDAR antagonist treatment.ConclusionThese findings offer crucial biochemical insights into the diverse impacts of NMDAR antagonists on dopamine dynamics and the distinct therapeutic mechanisms associated with ketamine in depression treatment. However, further investigation is imperative to pinpoint potential inconsistencies stemming from variances in drug type, dosage, or administration frequency.

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Chronic NMDA Antagonism Impairs Working Memory, Decreases Extracellular Dopamine, and Increases D1 Receptor Binding in Prefrontal Cortex of Conscious Monkeys

Cited by 84 publications

References 63 publications

Nicotine Normalizes Increased Prefrontal Cortical Dopamine D1 Receptor Binding and Decreased Working Memory Performance Produced by Repeated Pretreatment with MK-801: A PET Study in Conscious Monkeys

Nicotine Normalizes Increased Prefrontal Cortical Dopamine D1 Receptor Binding and Decreased Working Memory Performance Produced by Repeated Pretreatment with MK-801: A PET Study in Conscious Monkeys

Learning large‐scale spatial relationships in a maze and effects of MK‐801 on retrieval in the rhesus monkey

Effect of intermittent subchronic MK‐801 administration on dopamine synthesis capacity and responsiveness in the prefrontal cortex

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